THE COA ESTERS OF 2-METHYL-BRANCHED CHAIN FATTY-ACIDS AND OF THE BILE-ACID INTERMEDIATES DIHYDROXYCOPROSTANIC AND TRIHYDROXYCOPROSTANIC ACIDS ARE OXIDIZED BY ONE SINGLE PEROXISOMAL BRANCHED-CHAIN ACYL-COA OXIDASE IN HUMAN LIVER AND KIDNEY

Rat liver peroxisomes contain three acyl-CoA oxidases: palmitoyl-CoA o xidase, which oxidizes the CoA esters of straight chain fatty acids an d prostaglandins; pristanoyl-CoA oxidase, which oxidizes the CoA ester s of 2-methyl-branched fatty acids (e.g. pristanic acid); and trihydro xycoprostanoyl-CoA oxidase, which oxidizes the CoA esters of the bile acid intermediates di- and trihydroxycoprostanic acids (Van Veldhoven, P. P., Vanhove, G., Asselberghs, S., Eyssen, H. J., and Mannaerts, G. P. (1992) J. Biol. Chem. 267, 20065-20074). In the present report we demonstrate that human liver peroxisomes contain only two acyl-CoA oxi dases: palmitoyl-CoA oxidase, which oxidizes the CoA esters of straigh t chain fatty acids and prostaglandins, and a novel branched chain acy l-CoA oxidase, which oxidizes the CoA esters of 2-methyl-branched fatt y acids as well as those of the bile acid intermediates (which also po ssess a 2-methyl substitution in their side chains). The branched chai n acyl-CoA oxidase was purified to near homogeneity by means of column chromatography. It appeared to be a 70-kDa monomeric protein that did not cross-react with antisera raised against rat palmitoyl-CoA oxidas e and pristanoyl-CoA oxidase. No indication was found for the presence of a separate trihydroxycoprostanoyl-CoA oxidase in human liver. The branched chain acyl-CoA oxidase was present also in human kidney, sugg esting that it is expressed in other extrahepatic tissues as well. Our results explain a number of clinical-chemical observations made in ce rtain cases of peroxisomal beta-oxidation disorders.